A typical example of virus used to date as an agent for treatment of cancers is adenovirus, which is a vector for gene therapy. Adenovirus, however, merely functions as a vector for gene therapy, but a cytotoxic gene introduced therein is actually involved in treatment of cancers. Essentially, viruses infect specific cells to grow therein, thereby causing cell death to the infected cells with morphological changes, which are called cytopathic effects (CPEs). In recent years, a special virus, denominated oncolytic virus (wherein “onco” refers to cancer and “lytic” refers to lysis), has been known to exist. Oncolytic viruses grow in specific cancer cells, thereby exhibiting the strong CPE specific thereto and destroying them. The viruses, however, neither grow nor exhibit CPE in normal cells. To date, oncolytic viruses such as a reovirus specific to Ras-activated cancer cells (U.S. Pat. No. 6,344,195), an adenovirus variant specific to anticancer protein p53 defective cancer cells (DL1520; ONYX-015) (Post LE, Curr Opion Investig Drugs, 3(12), 1768-1772, 2000.), and a herpes virus variant specific to brain tumors (G207) (Toda M., Rabkin S D., Martuza R L., Hum Gene Ther, 9(15), 2177-2185, 1988) have been reported. Since oncolytic viruses exert their cytotoxity only for cancer cells but are harmless to normal cells, “anticancer virus therapy,” which is a new method for treatment of cancers employing the virus, is been becoming established. In contrast to surgery, which is a mainstream of current cancer treatment, the “anticancer virus therapy” is expected to be a less-invasive and more effective treatment. However, oncolytic viruses known heretofore have limited effects. In the case of the reovirus described above, for example, the virus can target only Ras-activated cancer cells, which account for approximately two-thirds of human cancers. Thus, the scope of application thereof is limited.
On the other hand, Sindbis virus is an RNA virus belonging to the genus Alphavirus of family Togaviridae, and is transmitted by mosquitoes that infect birds or mammals. Sindbis virus is a virus having a spherical shape with a diameter of approximately 40 nm to 80 nm, and it contains a single-stranded RNA genome and a nucleocapsid with a regular dodecahedron shape in its envelope. Sindbis virus AR339 strain was isolated from the mosquitoes (Culex pipiens and C. univittatus) in the north of Cairo, Egypt, in 1952 (Taylor, R M and H S Hurlbut; “Isolation of coxsackie-like viruses from mosquitoes” J. Egypt. Med. Assoc., 36, 489-494, 1953, etc.). Sindbis virus has so far been known to cause cytopathic effects upon various established mammalian cell lines (Griffin D E., 2001, Alphaviruses, 917-962, In Knipe D M and Howley P M (ed.), Fields virology, 4th ed., Lippincott-Raven Publishers, Philadelphia, Pa.), though its high specificity to cancer cells has not been reported. As in the case of adenovirus, there is nothing but an example that Sindbis virus was confirmed to have antitumor effects as a viral vector used for introduction of foreign genes (Jen-Chieh Tseng et al., “In Vivo Antitumor Activity of Sindvis Viral Vectors” Journal of the National Cancer Institute 94 (23), 1790-1801, Dec. 4, 2002).